Browse > Article
http://dx.doi.org/10.14456/apjcp.2016.56/APJCP.2016.17.7.3077

Anti-Tumor and Immunoregulatory Effects of Fermented Papaya Preparation (FPP: SAIDO-PS501)  

Murakami, Shinki (SAIDO Corporation)
Eikawa, Shingo (Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences)
Kaya, Savas (Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences)
Imao, Mitsuko (SAIDO Corporation)
Aji, Toshiki (Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.17, no.7, 2016 , pp. 3077-3084 More about this Journal
Abstract
Various beneficial effects have been described for fermented papaya preparation (FPP: SAIDO-PS501) based on its anti-oxidative and anti-inflammatory functions. The present study was designed to determine the effects of FPP on carcinogenesis in vivo, and immunomodulatory function in vitro. Mice were injected with RL male 1 cells subcutaneously or 3-methylcholantherene (MCA) intravenously to induce cancer and orally or intraperitoneally treated with FPP solution. Human peripheral blood mononuclear cells (PBMC) were obtained from healthy volunteers and patients with atopic dermatitis, treated with FPP, and subjected to measurement of cytokine production and changes in Foxp3-expressing regulatory T cell (Treg) stimulated with phytohemagglutinin (PHA). Administration of FPP suppressed tumor size and the incidence of malignancy. In vitro, treatment of PBMC with FPP induced IL-$1{\beta}$, $TNF{\alpha}$ and $IFN{\gamma}$ production. Moreover, FPP suppressed proliferation of PHA-stimulated Foxp3-expressing Treg. These results suggest that FPP has chemotherapeutic properties.
Keywords
Fermented papaya preparation; anti-tumorigenesis; immunoregulatory function; $interferon{\gamma}$; regulatory;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Proietti E, Tritarelli E, Gabriele L, et al (1993). Combined interleukin 1 beta/interleukin 2 treatment in mice: synergistic myelostimulatory activity and protection against cyclophosphamide-induced myelosuppression. Cancer Res, 53, 569-76.
2 Chen L, Zhang HY (2007). Cancer preventive mechanisms of the green tea polyphenol (-)-epigallocatechin-3-gallate. Molecules, 12, 946-57.   DOI
3 Ching LS, Mohamed S (2001). Alpha-tocopherol content in 62 edible tropical plants. J Agric Food Chem, 49, 3101-5.   DOI
4 De la Fuente M, Victor VM (2000). Anti-oxidants as modulators of immune function. Immunol Cell Biol, 78, 49-54.   DOI
5 DeLeo AB, Shiku H, Takahashi T, et al (1977). Cell surface antigens of chemically induced sarcomas of the mouse. I. Murine leukemia virus-related antigens and alloantigens on cultured fibroblasts and sarcoma cells: description of a unique antigen on BALB/c Meth A sarcoma. J Exp Med, 146, 720-734.   DOI
6 de Moreno de Leblanc A, Perdigon G (2004). Yogurt feeding inhibits promotion and progression of experimental colorectal cancer. Med Sci Monit, 10, 96-104.
7 Esumi N, Hunt B, Itaya T, et al (1991). Reduced tumorigenicity of murine tumor cells secreting gammma-interferon is due to nonspecific host responses and is unrelated to class I major histocompatibility complex expression. Cancer Res, 51, 1185-9.
8 Gantner BN, Simmons RM, Canavera SJ, et al (2003). Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J Exp Med, 197, 1107-17.   DOI
9 Rafter J (2003). Probiotics and colon cancer. Best Pract Res Clin Gastroenterol, 17, 849-59.   DOI
10 Reinhold U, Wehrmann W, Kukel S, et al (1990). Evidence that defective interferon-gamma production in atopic dermatitis patients is due to intrinsic abnormalities. Clin Exp Immunol, 79, 374-9.
11 Sagnia B, Fedeli D, Casetti R, et al (2014). Antioxidant and anti-inflammatory activities of extracts from cassia alata, eleusine indica, eremomastax speciosa, carica papaya and polyscias fulva medicinal plants collected in Cameroon. PLoS One, 9, 103999.   DOI
12 Sandle T (2013). Pharmaceutical product impurities: considering beta glucans. American Pharmaceutical Rev, 16, 5.
13 Sato H, Boyse EA, Aoki T, et al (1973). Leukemia-associated transplantation antigens related to murine leukemia virus. The X.1 system: immune response controlled by a locus linked to H-2. J Exp Med, 138, 593-606.   DOI
14 Taguchi T (1987). Clinical efficacy of lentinan on patients with stomach cancer: end point results of a four-year follow-up survey. Cancer Detect Prev, 1, 333-49.
15 Vesely MD, Kershaw MH, Schreiber RD, et al (2011). Natural innate and adaptive immunity to cancer. Annu Rev Immunol, 29, 235-71.   DOI
16 Hadley JS, Wang JE, Foster SJ, et al (2005). Peptidoglycan of Staphylococcus aureus upregulates monocyte expression of CD14, Toll-like receptor 2 (TLR2), and TLR4 in human blood: possible implications for priming of lipopolysaccharide signaling. Infect Immun, 73, 7613-9.   DOI
17 Harasym J, Oledzki R (2014). Effect of fruit and vegetable antioxidants on total antioxidant capacity of blood plasma. Nutrition, 30, 511-7.   DOI
18 Tokuyasu H, Takeda K, Kawasaki Y, et al (2010). High plasma concentration of beta-D-glucan after administration of sizofiran for cervical cancer. Int J Gen Med, 3, 273-7.
19 van Breemen RB, Pajkovic N (2008). Multitargeted therapy of cancer by lycopene. Cancer Lett, 269, 339-51.   DOI
20 van Hemert S, Meijerink M, Molenaar D, et al (2010). Identification of Lactobacillus plantarum genes modulating the cytokine response of human peripheral blood mononuclear cells. BMC Microbiol, 10, 293.   DOI
21 Iida N, Dzutsev A, Stewart CA, et al (2013). Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science, 342, 967-70.   DOI
22 Harutsumi M, Aji T, Manki A, et al (1995). Rejection of parental meth-a tumor on concomitant inoculation of meth-a cells infected retrovirally with the interferon-gamma gene into (balb/cxc57bl/6)f-1 mice. Int J Oncol, 7, 233-8.
23 Hino M, Kohchi C, Nishizawa T, et al (2005). Innate-immune therapy for lung carcinoma based on tissue-macrophage activation with lipopolysaccharide. Anticancer Res, 25, 3747-54.
24 Hiramoto K, Imao M, Sato E, et al (2008). Effect of fermented papaya preparation on dermal and intestinal mucosal immunity and allergic inflammations. J Sci of Food Agric, 88, 1151-7.   DOI
25 Imao K, Kameyama T, Ukai M (2001). PS-501, fermented papaya preparation improves scopolamine-induced amnesia in mice. Res Commun Pharmacol Toxicol, 6, 197-204.
26 Zhang J, Mori A, Chen Q, et al (2006). Fermented papaya preparation attenuates beta-amyloid precursor protein: beta-amyloid-mediated copper neurotoxicity in betaamyloid precursor protein and beta-amyloid precursor protein Swedish mutation overexpressing SH-SY5Y cells. Neuroscience, 143, 63-72.   DOI
27 Li TT, Ogino S, Qian ZR (2014). Toll-like receptor signaling in colorectal cancer: Carcinogenesis to cancer therapy. World J Gastroenterol, 20, 17699-708.   DOI
28 Mantovani G, Maccio A, Melis G, et al (2000). Restoration of functional defects in peripheral blood mononuclear cells isolated from cancer patients by thiol antioxidants alphalipoic acid and N-acetyl cysteine. Int J Cancer, 86, 842-7.   DOI
29 Mehdipour S, Yasa N, Dehghan G, et al (2006). Antioxidant potentials of Iranian Carica papaya juice in vitro and in vivo are comparable to alpha-tocopherol. Phytother Res, 20, 591-4.   DOI
30 Viaud S, Saccheri F, Mignot G, et al (2013). The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science, 342, 971-6.   DOI
31 Zhong L, Zhang X, Covasa M (2014). Emerging roles of lactic acid bacteria in protection against colorectal cancer. World J Gastroenterol, 20, 7878-86.   DOI
32 Kennedy AR (1995). The evidence for soybean products as cancer preventive agents. J Nutr, 125, 733-43.
33 Imao K, Wang H, Komatsu M, et al (1998). Free radical scavenging activity of fermented papaya preparation and its effect on lipid peroxide level and superoxide dismutase activity in iron-induced epileptic foci of rats. Biochem Mol Biol Int, 45, 11-23.
34 Kamangar F, Dores GM, Anderson WF (2006). Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol, 24, 2137-50.   DOI
35 Katagiri K, Itami S, Hatano Y, et al (1997). Increased levels of IL-13 mRNA, but not IL-4 mRNA, are found in vivo in peripheral blood mononuclear cells (PBMC) of patients with atopic dermatitis (AD). Clin Exp Immunol, 108, 289-94.   DOI
36 Murakami S, Takayama F, Egashira T, et al (2013). Fermented papaya preparation halts the progression of non-alcoholic steatohepatitis in rats. J Biophys Chem, 4, 84-90.   DOI
37 Miean KH, Mohamed S (2001). Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. J Agric Food Chem, 49, 3106-12.   DOI
38 Mohamed SK (2012). Antioxidant and immunostimulant effect of carica papaya linn. Aqueous extract in acrylamide intoxicated rats. Acta Inform Med, 20, 180-5.   DOI
39 Murakami S, Takayama F, Egashira T, et al (2012). Protective effect of fermented papaya preparation on stress-induced acute gastric mucosal lesion. J Biophys Chem, 3, 311-6.   DOI
40 Murata M, Thanan R, Ma N, et al (2012). Role of nitrative and oxidative DNA damage in inflammation-related carcinogenesis. J Biomed Biotechnol, 623019.
41 Krishna KL, Paridhavi M, Jagruti AP (2008). Review on nutritional, medicinal and pharmacological properties of Papaya (Carica papaya Linn.). Natur Prod Radia, 7, 364-73.
42 Nakamura Y, Morimitsu Y, Uzu T, et al (2000). A glutathione S-transferase inducer from papaya: rapid screening, identification and structure-activity relationship of isothiocyanates. Cancer Lett, 157, 193-200.   DOI
43 Noda Y, Murakami S, Mankura M, et al (2008). Inhibitory effect of fermented papaya preparation on hydroxyl radical generation from methylguanidine. J Clin Biochem Nutr, 43, 185-90.   DOI
44 Nakano H, Namatame K, Nemoto H, et al (1999). A multiinstitutional prospective study of lentinan in advanced gastric cancer patients with unresectable and recurrent diseases: effect on prolongation of survival and improvement of quality of life. Kanagawa Lentinan Research Group. Hepatogastroenterol, 46, 2662-8.
45 Nayak BS, Ramdeen R, Adogwa A, et al (2012). Wound-healing potential of an ethanol extract of Carica papaya (Caricaceae) seeds. Int Wound J, 9, 650-5.   DOI
46 Nguyen TT, Shaw PN, Parat MO, et al (2013). Anticancer activity of Carica papaya: a review. Mol Nutr Food Res, 57, 153-64.   DOI
47 Ohkusu-Tsukada K, Toda M, Udono H, et al (2010). Targeted inhibition of IL-10-secreting CD25- Treg via p38 MAPK suppression in cancer immunotherapy. Eur J Immunol, 40, 1011-21.   DOI
48 Onizuka S, Tawara I, Shimizu J, et al (1999). Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res, 59, 3128-33.
49 Osato JA, Santiago LA, Remo GM, et al (1993). Antimicrobial and antioxidant activities of unripe papaya. Life Sci, 53, 1383-9.   DOI
50 Otsuki N, Dang NH, Kumagai E, et al (2010). Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects. J Ethnopharmacol, 127, 760-7.   DOI
51 Pamer EG (2004). Immune responses to listeria monocytogenes. Nat Rev Immunol, 4, 812-3.   DOI
52 Basu A, Imrhan V (2007). Tomatoes versus lycopene in oxidative stress and carcinogenesis: conclusions from clinical trials. Eur J Clin Nutr, 61, 295-303.
53 Al-Shukaili A, Al-Abri S, Al-Ansari A, et al (2009). Effect of N-acetyl-L-cysteine on cytokine production by human peripheral blood mononuclear cells. Sultan Qaboos Univ Med J, 9, 70-4.
54 Andreesen R, Hennemann B, Krause SW (1998). Adoptive immunotherapy of cancer using monocyte-derived macrophages: rationale, current status, and perspectives. J Leukoc Biol, 64, 419-26.   DOI
55 Basu A, Haldar S (2008). Dietary isothiocyanate mediated apoptosis of human cancer cells is associated with Bcl-xL phosphorylation. Int J Oncol, 33, 657-63.
56 Carswell EA, Old LJ, Kassel RL, et al (1975). An endotoxininduced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA, 72, 3666-70.   DOI